小分子物质促进间充质干细胞神经向分化的研究进展
Advances in Small Molecules Promoting Neural Differentiation of Mesenchymal Stem Cells
DOI: 10.12677/acm.2025.153584, PDF,   
作者: 张聚鑫, 方 正, 田 峰:重庆医科大学口腔疾病与生物医学重庆市重点实验室,重庆;张富贵*:重庆医科大学附属口腔医院口腔颌面外科,重庆
关键词: 小分子物质间充质干细胞神经分化神经退行性疾病Small Molecule Mesenchymal Stem Cell Neuronal Differentiation Neurodegenerative Disease
摘要: 间充质干细胞(MSCs)是一种具有自我更新能力的细胞,这些细胞具有多项分化能力,且这些细胞表现出多种特征,如它们的分泌作用、向病变区域的迁移和免疫调节潜力,使它们成为神经退行性疾病细胞治疗的候选者。大量研究表明间充质干细胞可以经过刺激后分化为神经元。然而,尽管直接将原始且未分化的间充质干细胞移植到神经退行性疾病动物模型的多项试验取得了积极的结果,但一些研究表明,若在间充质干细胞移植治疗之前,应用组织工程学技术刺激间充质干细胞向神经元谱系分化,可以增强其获得的治疗效果。诱导间充质干细胞神经向分化的方法有多种,包括化学物质、生长因子、与神经谱系细胞共培养、基因转染、miRNA等,其中化学物质中小分子物质的效果尤为突出,采用一种或某几种小分子物质的组合可高效快捷地诱导间充质干细胞向神经向分化。因此,文章将论述回顾以往小分子物质促进间充质干细胞向神经系统细胞分化的研究进展,以为其应用于临床神经退行性疾病间充质干细胞治疗的研究提供基础。
Abstract: Mesenchymal stem cells (MSCs) possess self-renewal capacity, exhibit multiple differentiation potentials, and demonstrate key characteristics such as a secretory role, lesion-site migration, and immunomodulatory potential, rendering them strong candidates for neurodegenerative disease therapy. Numerous studies have demonstrated that MSCs can be effectively stimulated to differentiate into neurons. While positive results have been observed in studies directly transplanting primitive, undifferentiated MSCs into animal models of neurodegenerative disease, evidence suggests that preconditioning MSCs through tissue engineering techniques to induce neuronal differentiation can significantly enhance their therapeutic effects. Various strategies, such as chemical substances, growth factors, co-culture with neural cells, gene transfection, and miRNA, can induce the neural differentiation of MSCs. Among these, small molecules derived from chemical substances are particularly effective, as they efficiently and rapidly induce the neural differentiation of MSCs, either alone or in combination. This review aims to analyze advancements in the use of small molecules to promote MSC differentiation into neural cells, providing insights into their potential applications in MSC-based therapies for clinical neurodegenerative diseases.
文章引用:张聚鑫, 方正, 田峰, 张富贵. 小分子物质促进间充质干细胞神经向分化的研究进展[J]. 临床医学进展, 2025, 15(3): 42-47. https://doi.org/10.12677/acm.2025.153584

参考文献

[1] Kritsilis, M., Rizou, S.V., Koutsoudaki, P.N., Evangelou, K., Gorgoulis, V.G. and Papadopoulos, D. (2018) Ageing, Cellular Senescence and Neurodegenerative Disease. International Journal of Molecular Sciences, 19, Article 2937. [Google Scholar] [CrossRef] [PubMed]
[2] Perry, V.H., Nicoll, J.A.R. and Holmes, C. (2010) Microglia in Neurodegenerative Disease. Nature Reviews Neurology, 6, 193-201. [Google Scholar] [CrossRef] [PubMed]
[3] Temple, S. (2023) Advancing Cell Therapy for Neurodegenerative Diseases. Cell Stem Cell, 30, 512-529. [Google Scholar] [CrossRef] [PubMed]
[4] 赵晓璇, 刘帅祎, 邢政, 李庆雯, 褚晓蕾, 李奇. 周围神经损伤领域组织工程技术应用的研究热点与趋势变化[J]. 中国组织工程研究, 1-10.
https://link.cnki.net/urlid/21.1581.R.20250115.1402.014, 2025-01-20.
[5] 陈中, 郑阳, 张信成, 等. 退变髓核细胞修复及组织工程应用研究进展[J]. 医学综述, 2022, 28(7): 1267-1271.
[6] Ahmed, T.A. and Hincke, M.T. (2014) Mesenchymal Stem Cell-Based Tissue Engineering Strategies for Repair of Articular Cartilage. Histology and Histopathology, 29, 669-689. [Google Scholar] [CrossRef] [PubMed]
[7] Tsiapalis, D. and O’Driscoll, L. (2020) Mesenchymal Stem Cell Derived Extracellular Vesicles for Tissue Engineering and Regenerative Medicine Applications. Cells, 9, Article 991. [Google Scholar] [CrossRef] [PubMed]
[8] Quintiliano, K., Crestani, T., Silveira, D., Helfer, V.E., Rosa, A., Balbueno, E., et al. (2016) Neural Differentiation of Mesenchymal Stem Cells on Scaffolds for Nerve Tissue Engineering Applications. Cellular Reprogramming, 18, 369-381. [Google Scholar] [CrossRef] [PubMed]
[9] Reinhardt, P., Glatza, M., Hemmer, K., Tsytsyura, Y., Thiel, C.S., Höing, S., et al. (2013) Derivation and Expansion Using Only Small Molecules of Human Neural Progenitors for Neurodegenerative Disease Modeling. PLOS ONE, 8, e59252. [Google Scholar] [CrossRef] [PubMed]
[10] Gitler, A.D., Dhillon, P. and Shorter, J. (2017) Neurodegenerative Disease: Models, Mechanisms, and a New Hope. Disease Models & Mechanisms, 10, 499-502. [Google Scholar] [CrossRef] [PubMed]
[11] Dugger, B.N. and Dickson, D.W. (2017) Pathology of Neurodegenerative Diseases. Cold Spring Harbor Perspectives in Biology, 9, a028035. [Google Scholar] [CrossRef] [PubMed]
[12] 吴卉, 靳翠红. 神经退行性疾病发病机制的研究进展[J]. 毒理学杂志, 2018, 32(6): 484-488. [Google Scholar] [CrossRef
[13] Ricci, C. (2024) Neurodegenerative Disease: From Molecular Basis to Therapy. International Journal of Molecular Sciences, 25, Article 967. [Google Scholar] [CrossRef] [PubMed]
[14] Zhou, Z.D. and Kihara, A.H. (2024) Neurodegenerative Diseases: Molecular Mechanisms and Therapies 2nd Edition. International Journal of Molecular Sciences, 25, Article 11334. [Google Scholar] [CrossRef] [PubMed]
[15] Marcos-Rabal, P., González-Fuentes, J., Castro-Vázquez, L., Lozano, M.V., Rodríguez-Robledo, V., Santander-Ortega, M.J., et al. (2021) Neurodegenerative Diseases: A Multidisciplinary Approach. Current Pharmaceutical Design, 27, 3305-3336. [Google Scholar] [CrossRef] [PubMed]
[16] Xu, Q., Hou, W., Zhao, B., Fan, P., Wang, S., Wang, L., et al. (2024) Mesenchymal Stem Cells Lineage and Their Role in Disease Development. Molecular Medicine, 30, Article No. 207. [Google Scholar] [CrossRef] [PubMed]
[17] Liu, J., Gao, J., Liang, Z., Gao, C., Niu, Q., Wu, F., et al. (2022) Mesenchymal Stem Cells and Their Microenvironment. Stem Cell Research & Therapy, 13, Article No. 429. [Google Scholar] [CrossRef] [PubMed]
[18] Kern, S., Eichler, H., Stoeve, J., Klüter, H. and Bieback, K. (2006) Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue. Stem Cells, 24, 1294-1301. [Google Scholar] [CrossRef] [PubMed]
[19] Vasanthan, J., Gurusamy, N., Rajasingh, S., Sigamani, V., Kirankumar, S., Thomas, E.L., et al. (2020) Role of Human Mesenchymal Stem Cells in Regenerative Therapy. Cells, 10, Article 54. [Google Scholar] [CrossRef] [PubMed]
[20] Klimczak, A. (2024) Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration—Part II. International Journal of Molecular Sciences, 25, Article 4937. [Google Scholar] [CrossRef] [PubMed]
[21] 周红, 阮英, 吴喆, 等. 干细胞治疗中枢神经退行性疾病的研究进展[J]. 湖北科技学院学报(医学版), 2023, 37(2): 177-180. [Google Scholar] [CrossRef
[22] Azizi, S.A., Stokes, D., Augelli, B.J., DiGirolamo, C. and Prockop, D.J. (1998) Engraftment and Migration of Human Bone Marrow Stromal Cells Implanted in the Brains of Albino Rats—Similarities to Astrocyte Grafts. Proceedings of the National Academy of Sciences of the United States of America, 95, 3908-3913. [Google Scholar] [CrossRef] [PubMed]
[23] 张煜超, 王芳芳, 李周敏, 等. 小分子药物人工抗原的合成与鉴定研究进展[J]. 药物分析杂志, 2014, 34(6): 947-951.
[24] 林桃燕, 郑萍. 小分子靶向药物临床应用药学指引[J]. 中国医院用药评价与分析, 2024, 24(11): 1281-1296, 1302. [Google Scholar] [CrossRef
[25] Rajabi, H., Hosseini, V., Rahimzadeh, S., Seyfizadeh, N., Aslani, S. and Abhari, A. (2019) Current Status of Used Protocols for Mesenchymal Stem Cell Differentiation: A Focus on Insulin Producing, Osteoblast-Like and Neural Cells. Current Stem Cell Research & Therapy, 14, 570-578. [Google Scholar] [CrossRef] [PubMed]
[26] Alexanian, A.R., Liu, Q. and Zhang, Z. (2013) Enhancing the Efficiency of Direct Reprogramming of Human Mesenchymal Stem Cells into Mature Neuronal-Like Cells with the Combination of Small Molecule Modulators of Chromatin Modifying Enzymes, SMAD Signaling and Cyclic Adenosine Monophosphate Levels. The International Journal of Biochemistry & Cell Biology, 45, 1633-1638. [Google Scholar] [CrossRef] [PubMed]
[27] Madhu, V., Dighe, A.S., Cui, Q. and Deal, D.N. (2015) Dual Inhibition of Activin/Nodal/TGF‐β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells. Stem Cells International, 2016, Article ID: 1035374. [Google Scholar] [CrossRef] [PubMed]
[28] Park, J., Lee, N., Lee, J., Choe, E.K., Kim, M.K., Lee, J., et al. (2017) Small Molecule-Based Lineage Switch of Human Adipose-Derived Stem Cells into Neural Stem Cells and Functional Gabaergic Neurons. Scientific Reports, 7, Article No. 10166. [Google Scholar] [CrossRef] [PubMed]
[29] Hu, Y., Li, X., Huang, G., Wang, J. and Lu, W. (2019) Fasudil May Induce the Differentiation of Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells via the Wnt/β-Catenin Pathway. Molecular Medicine Reports, 19, 3095-3104. [Google Scholar] [CrossRef] [PubMed]
[30] Heng, B.C., Jiang, S., Yi, B., Gong, T., Lim, L.W. and Zhang, C. (2019) Small Molecules Enhance Neurogenic Differentiation of Dental-Derived Adult Stem Cells. Archives of Oral Biology, 102, 26-38. [Google Scholar] [CrossRef] [PubMed]